The CD1 is a system of proteins encoded by five genes, CD1A-E, which, although homologous to the classical MHC molecules, are distinct in their structure and function. There is increasing recognition that the CD1 molecules may serve a unique role as a third arm of antigen presentation distinct from both MHC class I and class II. CD1 combines structural and functional elements of both systems for presentation of distinct types of non-peptide antigens and represents an integral component of immune response. CD1b and CD1c have been shown to present antigens derived from mycolipid moieties from Mycobacterium tuberculosis, and it is speculated that CD1 family members are involved in presentation of processed microbial pathogens as antigens. In addition, the CD1 gene family expressed by particular types of antigen presenting cells may regulate cytokine tone through activation of distinct subsets of T-lymphocytes. Indeed, previous studies have shown that CD1 is expressed by the cellular elements of the gut and liver. Whereas CD1a-c are expressed by professional antigen presenting cells of the intestinal lamina propria, CD1d is expressed by intestinal epithelial cells and hepatocytes. The restricted localization of CD1d taken together with the unique biochemical structure of CD1d suggest that the immunologic role for CD1d in the gastrointestinal tract and liver is likely to be distinctive. The two specific aims as outlined below are focused on exploring both the structural and biologically functional characteristics of CD1d in intestine. AIM 1 is derived from previous studies which have shown that CD1d transfected intestinal epithelial cells express two distinct biochemical forms of CD1d on the cell surface. Therefore, the first aim is to define the biologic consequences of the interactions between different biochemical forms of CD1d and T cell subpopulations. AIM 2 is derived from previous studies using CD1d knockout mice that demonstrated the protective role of CD1d in chemically-induced colitis. Given the hypothesis that CD1d may be important in processing of microbial antigens and in downregulating inflammatory response, enteric bacteria will be used to infect CD1d knockout mice to understand the in vivo role of CD1d in bacterial infection.